Project Summary As the average age of the US population increases and chronic conditions are becoming more prevalent, there is a need to improve the effectiveness of disease prevention, to improve access to healthcare, and to sustain healthy independent living. At the same time, there is an increased availability of new technologies and an ever-improving health information technology infrastructure with >90% of American adults owning a cell phone and 55% having a Smart-Phone. Evolution of these wireless devices is expected to mark a new era in medicine and a transition from population-level health care to individualized medicine, that promises to improve patient-provider communication, adherence to treatment and self-management of chronic diseases in under-served populations. At the same time, despite the availability of a multitude of evidence-based therapies for the treatment of heart failure (HF), a chronic disease, the burden of HF on the US population remains unacceptably high, with an estimated 1 million admissions per year, the majority of which involve the elderly. Moreover, HF readmission rates, are a marker of worse prognosis and represent a significant healthcare expenditure and performance measure for payers, while efforts to reduce the burden of rehospitalization using conventional markers have been largely ineffective. Therefore, new, low-cost, easy-to-deploy technologies are needed to meet the clinical need for long- term (>1-2 days) respiratory and cardiac monitoring of the ambulatory patients, especially those that do not have easy access to Hospital-based health-care. The central goal of this R21 application is to investigate the hypothesis that one may develop methods for estimating the respiratory rate (RR), tidal volume (TV) and evolving ischemia, by recording cardiac electrical activity from the body surface, measuring the beat-to-beat variability in the morphology of electrocardiographic waveforms, and using the measured beat-to-beat variability to estimate the RR, TV and the severity of ischemia using the on-board computing power of a Smart- Phone, without the need of additional hardware. To achieve the aims of this proposal we will (i) develop and validate a medical-grade, smart-phone based, 12-lead wireless ECG system to measure the respiratory rate and tidal volume; (ii) demonstrate that ischemia can be accurately estimated by a smart-phone from wirelessly transmitted ECG signals. Success of this proposal will help develop a novel patient-based diagnostic device, that will improve ambulatory patient monitoring (especially those that live in under-served areas), without the need of specialized hardware.